PROTECT Study: 35 Months of Everolimus Monotherapy vs. Calcineurin Inhibitor-Based Therapy Showed To Be a Safe Alternative with Superior Renal Function in Liver Transplant Recipients, The
University Hospital Regensburg, Regensburg, Germany
Essen University Hospital, Essen, Germany
Hannover Medical School (MHH), Hannover, Germany
University Hospital Tuebingen, Tuebingen, Germany
Jena University Hospital, Jena, Germany
Charite University Medical Center Berlin, Berlin, Germany
University Hospital Heidelberg, Heidelberg, Germany
University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Novartis Pharma GmbH, Nuremberg, Germany
Meeting: 2013 American Transplant Congress
Abstract number: 321
Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function. The PROTECT study showed that conversion from CNI to the mTOR-inhibitor everolimus (EVR) at 4 weeks after liver transplantation (LTx) achieves better renal function at 11 months (M) without compromising efficacy. Results of the PROTECT extension period up to 35 M are presented.
In this multicenter, prospective, open label study LTx patients with initial good renal function (calculated GFR ≥50mL/min) 4-8 weeks after liver transplantation (LTx) were randomized to either continued CNI treatment (n=96; standard CNI dose tacrolimus or cyclosporine] ±steroids) or switch to EVR ± steroids (n=98). EVR was adjusted to target trough level of 5-12ng/mL and CNI was withdrawn stepwise until week 16 post randomization. Patients who completed the 11 month core study were followed up to month 35 in the extension phase.
A total of 81 patients (EVR, n=41; CNI, n=40) continued in the follow-up phase. From M12 to M35 further renal function deterioration was observed in the CNI-arm while renal function remained stable in patients receiving EVR. Difference in eGFR between EVR and CNI: Cockcroft-Gault M11: -6.8 mL/min [p=0.240]; M23: -9.8 ml/min [p=0.104]; M35: -10.5 mL/min [p=0.096) and Nankivell formula (M11: -6.6 mL/min [p=0.084]; M23: -8.8 ml/min [p=0.039];M35: -10.5 mL/min [p=0.015]). At M35 there were no significant differences in rates of mortality (EVR: 4.3% vs. CNI: 10.0%, p=0.535), biopsy-proven acute rejection (24.4% vs. 15.8%, p=0.434), and efficacy failure (29.8% vs. 28.2%, p=0.903) were similar. Discontinuation of study treatment due to an AE during the follow-up period was observed in 5 (12.2%) patients on EVR vs. 6 (15.0%) in the CNI group.
Conversion from CNI-based to EVR-based immunosuppression proved to be a safe alternative post-LTx and potentially reduces the risk of end-stage renal disease.
Schlitt, H.: Grant/Research Support, Everolimus. Kaiser, G.: Grant/Research Support, Everolimus. Richter, N.: Grant/Research Support, Everolimus. Heyne, N.: Grant/Research Support, Everolimus. Rauchfuss, F.: Grant/Research Support, Everolimus. Neuhaus, P.: Grant/Research Support, Everolimus. Schemmer, P.: Grant/Research Support, Everolimus. Fischer, L.: Grant/Research Support, Everolimus. Paulus, E.: Employee, Novartis. Mertens, M.: Employee, Novartis. Sterneck, M.: Grant/Research Support, Everolimus.
To cite this abstract in AMA style:
Schlitt H, Kaiser G, Richter N, Heyne N, Rauchfuss F, Neuhaus P, Schemmer P, Fischer L, Paulus E, Mertens M, Sterneck M. PROTECT Study: 35 Months of Everolimus Monotherapy vs. Calcineurin Inhibitor-Based Therapy Showed To Be a Safe Alternative with Superior Renal Function in Liver Transplant Recipients, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/protect-study-35-months-of-everolimus-monotherapy-vs-calcineurin-inhibitor-based-therapy-showed-to-be-a-safe-alternative-with-superior-renal-function-in-liver-transplant-recipients-the/. Accessed May 17, 2025.« Back to 2013 American Transplant Congress